Lin28 recruits the TUTase Zcchc11 to inhibit let-7 maturation in mouse embryonic stem cells

被引：408

作者：

Hagan, John P. ^{[1
,2
]}

Piskounova, Elena ^{[1
]}

Gregory, Richard I. ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol,Stem Cell Program, Childrens Hosp Boston,Harvard Med Sch, Boston, MA 02115 USA

[2] Ohio State Univ, Med Ctr, Coll Med, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2009年 / 16卷 / 10期

关键词：

GENOME-WIDE ASSOCIATION; MESSENGER-RNA; IDENTIFICATION; LOCI; AGE; MICRORNAS; LIN-28; OLIGOURIDYLATION; URIDYLATION; PATHWAYS;

D O I：

10.1038/nsmb.1676

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Lin28 and Lin28B, two developmentally regulated RNA-binding proteins and likely proto-oncogenes, selectively inhibit the maturation of let-7 family microRNAs (miRNAs) in embryonic stem cells and certain cancer cell lines. Moreover, let-7 precursors (pre-let-7) were previously found to be terminally uridylated in a Lin28-dependent fashion. Here we identify Zcchc11 ( zinc finger, CCHC domain containing 11) as the 3' terminal uridylyl transferase (TUTase) responsible for Lin28-mediated pre-let-7 uridylation and subsequent blockade of let-7 processing in mouse embryonic stem cells. We demonstrate that Zcchc11 activity is UTP-dependent, selective for let-7 and recruited by Lin28. Furthermore, knockdown of either Zcchc11 or Lin28, or overexpression of a catalytically inactive TUTase, relieves the selective inhibition of let-7 processing and leads to the accumulation of mature let-7 miRNAs and repression of let-7 target reporter genes. Our results establish a role for Zcchc11-catalyzed pre-let-7 uridylation in the control of miRNA biogenesis.

引用

页码：1021 / U33

页数：6

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